miR-26a attenuates cardiac apoptosis and fibrosis by targeting ataxia-telangiectasia mutated in myocardial infarction
© 2020 Wiley Periodicals, Inc..
Apoptosis and fibrosis play a vital role in myocardial infarction (MI) induced tissue injury. Although microRNAs have been the focus of many studies on cardiac apoptosis and fibrosis in MI, the detailed effects of miR-26a is needed to further understood. The present study demonstrated that miR-26a was downregulated in ST-elevation MI (STEMI) patients and oxygen-glucose deprivation (OGD)-treated H9c2 cells. Downregulation of miR-26a was closely correlated with the increased expression of creatine kinase, creatine kinase-MB and troponin I in STEMI patients. Further analysis identified that ataxia-telangiectasia mutated (ATM) was a target gene for miR-26a based on a bioinformatics analysis. miR-26a overexpression effectively reduced ATM expression, apoptosis, and apoptosis-related proteins in OGD-treated H9c2 cells. In a mouse model of MI, the expression of miR-26a was significantly decreased in the infarct zone of the heart, whereas apoptosis and ATM expression were increased. miR-26a overexpression effectively reduced ATM expression and cardiac apoptosis at Day 1 after MI. Furthermore, we demonstrated that overexpression of miR-26a improved cardiac function and reduced cardiac fibrosis by the reduced expression of collagen type I and connective tissue growth factor (CTGF) in mice at Day 14 after MI. Overexpression of miR-26a or ATM knockdown decreased collagen I and CTGF expression in cultured OGD-treated cardiomyocytes. Taken together, these data demonstrate a prominent role for miR-26a in linking ATM expression to ischemia-induced apoptosis and fibrosis, key features of MI progression. miR-26a reduced MI development by affecting ATM expression and could be targeted in the treatment of MI.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:235 |
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| Enthalten in: |
Journal of cellular physiology - 235(2020), 9 vom: 28. Sept., Seite 6085-6102 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chiang, Ming-Hsien [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.03.2021 Date Revised 11.03.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/jcp.29537 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM305862065 |
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| 100 | 1 | |a Chiang, Ming-Hsien |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a miR-26a attenuates cardiac apoptosis and fibrosis by targeting ataxia-telangiectasia mutated in myocardial infarction |
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| 520 | |a © 2020 Wiley Periodicals, Inc. | ||
| 520 | |a Apoptosis and fibrosis play a vital role in myocardial infarction (MI) induced tissue injury. Although microRNAs have been the focus of many studies on cardiac apoptosis and fibrosis in MI, the detailed effects of miR-26a is needed to further understood. The present study demonstrated that miR-26a was downregulated in ST-elevation MI (STEMI) patients and oxygen-glucose deprivation (OGD)-treated H9c2 cells. Downregulation of miR-26a was closely correlated with the increased expression of creatine kinase, creatine kinase-MB and troponin I in STEMI patients. Further analysis identified that ataxia-telangiectasia mutated (ATM) was a target gene for miR-26a based on a bioinformatics analysis. miR-26a overexpression effectively reduced ATM expression, apoptosis, and apoptosis-related proteins in OGD-treated H9c2 cells. In a mouse model of MI, the expression of miR-26a was significantly decreased in the infarct zone of the heart, whereas apoptosis and ATM expression were increased. miR-26a overexpression effectively reduced ATM expression and cardiac apoptosis at Day 1 after MI. Furthermore, we demonstrated that overexpression of miR-26a improved cardiac function and reduced cardiac fibrosis by the reduced expression of collagen type I and connective tissue growth factor (CTGF) in mice at Day 14 after MI. Overexpression of miR-26a or ATM knockdown decreased collagen I and CTGF expression in cultured OGD-treated cardiomyocytes. Taken together, these data demonstrate a prominent role for miR-26a in linking ATM expression to ischemia-induced apoptosis and fibrosis, key features of MI progression. miR-26a reduced MI development by affecting ATM expression and could be targeted in the treatment of MI | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Liang, Chan-Jung |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Lung-Chun |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yi-Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Ching-Chang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ying-Hsien |e verfasserin |4 aut | |
| 700 | 1 | |a Kao, Hsien-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yu-Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Ke, Shin-Rong |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Chiang-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Mao-Shin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yuh-Lien |e verfasserin |4 aut | |
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